CERAD, The Consortium to Establish a Registry for Alzheimer’s Disease
 
CERAD PUBLICATIONS
1988 - 2003

Clinical
Reliable information on the rate of progression of cognitive impairment was obtained in a well-characterized group of patients with AD who were followed using standardized CERAD assessments. Rate of decline was slower for patients with less severe dementia. Significant weight loss was found to be more frequent in patients than in controls. CERAD studies also reported the impact of depression on AD, those with early- vs. late-onset dementia, and comparisons of patients with AD and those with schizophrenia.

Clark CM, Sheppard L, Fillenbaum GG, et al. Variability in annual Mini-Mental State score in patients with probable Alzheimer's disease: a clinical perspective of data from CERAD. Arch Neurol 1999;56:857-962.

Davidson MD, Harvey P, Welsh KA, et al. Cognitive functioning in late-life schizophrenia: a comparison of elderly schizophrenic patients and patients with Alzheimer's disease. Am J Psychiatry 1996;153:1274-1279.

Fillenbaum GG, Beekly D, Edland SD, et al. Consortium to Establish a Registry for Alzheimer's Disease (CERAD): Development, data base structure, and selected findings. Top Health Inform Management 1997;18:47-58.

Galasko D, Edland SD, Morris JC, et al. CERAD Part XI. Clinical milestones In patients with Alzeimer's disease followed over three years. Neurology 1995;45:1451-1455.

Heyman A, Fillenbaum G, Mirra SS. CERAD: Clinical, neuropsychological, and neuropathological components. Aging: Clin Exp Res 1991;2:416-424.

Heyman A, Fillenbaum G, Nash F, eds. Consortium to Establish a Registry for Alzheimer's Disease: The CERAD experience. Neurology 1997;49 (suppl 3, whole issue).

Koss E, Edland S, Fillenbaum G, et al. Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer's disease: a CERAD analysis, Part XII. Neurology 1996;46:136-141.

Koss E, Peterson B, Fillenbaum GG. Determinants of attrition in a natural history study of Alzheimer disease. Alzheimer Dis Assoc Disord 1999;13:209-215.

McDaniel K, Edland S, Heyman A, et al. Relationship between level of insight and severity of dementia in Alzheimer's disease. Alzheimer Dis Assoc Disord 1995;9:101-104.

Morris JC, Mohs RC, Rogers H, et al. CERAD: clinical and neuropsychological assessment of Alzheimer's disease. Psychopharmacol Bull 1988;4:641-652.

Morris JC, Heyman A, Mohs RC, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Part I. Clinical and neuropsychological assessment of Alzheimer's disease. Neurology 1989;39:1159-1165.

Morris JC, Edland S, Clark CM, et al. Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Part IV. Rates of cognitive change, a longitudinal assessment of probable Alzheimer's disease. Neurology 1993;43:2457-2465.

Morris JC. Clinical and neuropathological findings from CERAD. In: Becker R, Giacobini E, eds. Alzheimer disease: from molecular biology to therapy. Birkhauser, Boston 1997:8-12.

Weiner M, Edland S, Luszczynska H. Prevalence and incidence of major depression in Alzheimer's disease. Am J Psychiatry 494;151:1006-1009.

White H, Pieper C, Schmader K, et al. Weight change in Alzheimer's disease. J Am Geriatr Soc 1996;44:265-272.

White H, Pieper C, Schmader K, et al. A longitudinal analysis of weight change in Alzheimer's disease [letter]. J Am Geriatr Soc 1997;45:531-532.

Neuropsychology
The Neuropsychology Battery developed by CERAD includes tests of verbal fluency (naming animals); a modified 15-item Boston Naming Test; Mini-Mental State Examination; word list memory, recall, and recognition; constructional praxis; and recall of constructional praxis. Word list recall was found to distinguish best between AD patients and normal controls.

Fillenbaum G, Wilkinson W, Welsh K, et al. Discrimination between stages of Alzheimer's disease with subsets of Mini-Mental State Examination items: an analysis of CERAD data. Arch Neurol 1994;51:916-921.

Henderson VW, Buckwalter JG. Cognitive deficits of men and women with Alzheimer's disease. Neurology 1994;44:90-96.

Welsh K, Butters N, Hughes JP, et al. Detection of abnormal memory decline in mild cases of Alzheimer's disease using CERAD neuropsychological measures. Arch Neurol 1991;48:278-281.

Welsh K, Butters N, Hughes JP, et al. Detection and staging of dementia in Alzheimer's disease - use of the neuropsychological measures developed for CERAD. Arch Neurol 1992;49:448-452.

Welsh K, Butters N, Mohs RC, et al. CERAD Part V: a normative study of the neuropsychological battery. Neurology 1994;44:609-614.

Fillenbaum GG, Unverzagt FW, Ganguli M, Welsh-Bohmer KA, Heyman A. The CERAD neuropsychological battery: performance of representative community and tertiary care samples of African American and European American elderly. In Ferraro FR (ed.) Minority and cross cultural aspects of neuropsychological assessment. Swets and Zeitlinger, Lisse, NL, 2002.

Neuroimaging
Although the CERAD attempt to standardize neuroimaging measures of AD suggests that uniform reading of brain scans at any one clinical site was possible, uniform reading across multiple sites proved difficult to achieve.

Davis PC, Gray L, Albert M, et al. CERAD Part III: reliability of a standardized MRI evaluation of Alzheimer's disease. Neurology 1992;42:1676-1680.

Davis PC, Gearing M, Gray L, et al. The CERAD experience, Part VIII: neuroimaging-neuropathology correlates of temporal lobe changes in Alzheimer's disease. Neurology 1995;45:178-179.

Neuropathology
Findings obtained using the CERAD neuropathology protocol confirmed the clinical diagnosis of AD in 87% of autopsied CERAD patients. This widely-used protocol has since been modified for use by general pathologists for the diagnosis of dementia. (See also section on Associated Dementias.)


Cochran EJ, Gostanian OM, Mirra SS. Autopsy practices at CERAD and Alzheimer disease center sites: a survey of neuropathologists. Alzheimer Dis Assoc Disord 1995;9:203-207.

Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: the CERAD experience, Part XV. Neurology 1996;46:1592-1596.

Fillenbaum GG, Huber MS, Beekly D, et al. CERAD Part XIII. Obtaining autopsy in Alzheimer's disease. Neurology 1996;46:142-145.

Gearing M, Mirra SS, Hedreen J, et al. CERAD Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer's disease. Neurology 1995;45:461-466.

Mirra SS, Heyman A, McKeel DW, et al. CERAD Part II. Standardization of the neuropathological assessment of Alzheimer's disease. Neurology 1991;41:479-486.

Mirra SS, Hart MN, Terry RD. Making the diagnosis of Alzheimer's disease: a primer for practicing pathologists. Arch Pathol Lab Med 1993;117:132-144.

Mirra SS. Neuropathological assessment of Alzheimer's disease: the experiences of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Internat Psychogeriatrics 1997;9:263-268:Discussion 269-272.

Mirra SS, Gearing M, Sumi SM, et al. The neuropathology assessment of Alzheimer's disease and related dementias: the CERAD experience. In Corain B, et al., eds. Alzheimer's disease: advances in clinical and basic research. John Wiley & Sons Ltd, 1993:207-211.

Mirra SS, Gearing M, McKeel DW, et al. Interlaboratory comparison of neuropathology assessments in Alzheimer's disease: a CERAD study. J Neuropath Exp Neurol 1994;53(3):303-315.

Mirra SS. The CERAD neuropathology protocol and consensus recommendations for the postmortem diagnosis of Alzheimer's disease: a commentary. Neurobiol Aging 1997;18(suppl):S91-S94.

Olichney JM, Ellis RJ, Katzman R, et al. Types of cerebrovascular lesions associated with severe cerebral amyloid angiopathy in Alzheimer's disease. Ann NY Acad Sci 1997;826:493-497.


Minority Studies

In CERAD, as in other longitudinal studies, recruitment and retention of African American subjects often required special measures. When age, education, and severity of disease at entry were controlled, race was found to have only a very mild effect on progression of dementia.

Ballard E, Nash F, Raiford K, et al. Recruitment of black elderly for clinical research studies of dementia: the CERAD experience. Gerontologist 1993;33:561-565.

Fillenbaum GG, Peterson B, Welsh-Bohmer KA, et al. Progression of Alzheimer's disease in black and white patients: the CERAD experience, Part XVI. Neurology 1998;51:154-158.

Fillenbaum GG, Heyman A, Huber MS, Ganguli M, Unverzagt FW. Performance of elderly African American and White community residents on the CERAD Neuropsychological Battery. JINS 2001;7:502-509.

Welsh K, Ballard E, Nash F, et al. Issues affecting minority participation in research studies of Alzheimer's disease. Alzheimer Dis Assoc Disord 1994;8 Suppl 4:38-48.

Welsh K, Fillenbaum GG, Wilkinson W, et al. Neuropsychological test performance in African-American and white patients with Alzheimer's disease. Neurology 1995;45:2207-2211.

Health Economics
AD is reported to be the third most expensive disease in the US, after heart disease and cancer. There are few published studies on Medicare-reimbursed services for patients with an accurate diagnosis of AD. CERAD studies indicated that the frequency and duration of hospitalization were greater for AD subjects than for matched controls. These studies further indicate that multiple years of Medicare-based data are needed to identify persons with AD.

Fillenbaum G, Heyman A, Peterson B, Pieper C, Weiman AL. Frequency and duration of hospitalization of patients with AD based on Medicare data: CERAD XX. Neurology 2000;54:740-743.

Fillenbaum G, Heyman A, Peterson BL, Pieper CF, Weiman AL. Use and cost of hospitalization of patients with AD by stage and living arrangement: CERAD XXI. Neurology 2001;56:201-206.

Fillenbaum G, Heyman A, Peterson BL, Pieper CF, Weiman AL. Use and cost of outpatient visits of AD patients: CERAD XXII. Neurology 2001;56:1706-1711.

Taylor DH, Fillenbaum GG, Ezell ME. The accuracy of Medicare claims data in identifying Alzheimer's disease. J Clin Epidemiol 2002;55:929-937.

Family History
In our study comparing the families of 118 patients with AD and their nondemented spouses, we found a significantly greater risk for AD among families of patients than among those of controls. There was also a greater risk of AD among female relatives than among males.

Edland SD, Silverman JM, Peskind ER, et al. Increased risk of dementia in mothers of Alzheimer's disease cases: evidence for maternal inheritance. Neurology 1996;47:254-256.

Silverman J, Raiford K, Edland S, et al. CERAD Part VI: family history assessment: a multi-center study of relatives of AD probands and non-demented spouse controls. Neurology 1994;44:1253-1259.

Outcomes
Age, sex, and severity of dementia were found to be the major predictors of survival of patients with AD, whereas race, education, and marital status were not important predictors. The major predictors of time to nursing home admission were sex, age, marital status (men only), and severity of dementia. Death certificates were found to be poor sources of information regarding the presence of dementia, since dementia was not mentioned in nearly a third of the death certificates of CERAD patients who had an overt clinical diagnosis of AD.

Heyman A, Peterson B, Fillenbaum G, et al. CERAD Part XIV: demographic and clinical predictors of survival in patients with Alzheimer's disease. Neurology 1996;46:656-660.

Heyman A, Peterson B, Fillenbaum G, et al. Predictors of time to institutionalization of patients with Alzheimer's disease. The CERAD experience, Part XVII. Neurology 1997;48:1304-1309.

Raiford K, Anton-Johnson S, Haycox Z, et al. CERAD Part VII: accuracy of reporting dementia on death certificates of patients with Alzheimer's disease. Neurology 1994;44:2208-2209.

Associated Dementias
Neuropathologic examination of the brains of CERAD cases with autopsy-confirmed AD disclosed coexisting lesions of Parkinson’s disease in 21% of them, and of cerebrovascular disease in an additional 28%. Patients with cerebrovascular lesions tended to be older, more severely demented, and performed more poorly on neuropsychology testing.

Clark CM, Ewbank D, Lerner A, et al. The relationship between extrapyramidal signs and cognitive performance in patients with Alzheimer's disease enrolled in the CERAD study. Neurology 1997;49:70-75.

Heyman A, Fillenbaum GG, Welsh-Bohmer KA, et al. Cerebral infarcts in patients with autopsy-proven Alzheimer's disease. CERAD. Part XVIII. Neurology 1998;51:159-162.

Heyman A, Fillenbaum GG, Gearing M, et al. Comparison of Lewy body variant of Alzheimer's disease with pure Alzheimer's disease: CERAD Part XIX. Neurology 1999;52:1839-1844.

Hulette C, Mirra SS, Wilkinson W, et al. CERAD Part IX: a prospective cliniconeuropathologic study of Parkinson's features in Alzheimer's disease. Neurology 1995;45:1991-1995.

Hulette C, Nochlin D, McKeel D, et al. Clinical-neuropathologic findings in multi-infarct dementia: a report of six autopsied cases. Neurology 1997;48:668-672.

Welsh-Bohmer KA, Gearing M, Saunders AM, et al. Apolipoprotein E genotypes in a neuropathological series from CERAD. Ann Neurol 1997;42:319-325.

Behavioral Studies
The CERAD Behavior Rating Scale for Dementia (BRSD) identified eight behavioral domains that may be related to AD, including agitation, depression, and hallucinatory phenomena. Both a full (46 item) and a short (17 item) version of this scale are available.

Patterson MB, Mack JL, Mackell JA, et al. A longitudinal study of behavioral pathology across five levels of dementia severity in Alzheimer's disease: the CERAD Behavior Rating Scale for Dementia. Alzheimer Dis Assoc Disorder 1997;11:S40-S44.

Patterson MB, Mack JL. CERAD Behavioral Rating Scale for Dementia (BRSD). Alzheimer Dis Assoc Disord 1997;11:S40-S44.

Tariot PN, Mack JL, Patterson MB, et al. The CERAD Behavior Rating Scale for Dementia. Am J Psychiatry 1995;152:1349-1357.

Tariot PN. CERAD Behavior Rating Scale for Dementia. Int Psychogeriatr 1996;8(suppl 3):317-320.

Mack JL, Patterson MB, Tariot PN. Behavior Rating Scale for Dementia: Development of test scales and presentation of data for 555 individuals with disease. J Geriatr Psychiatry Neurol 1999;12:211-223.


Studies In Foreign Languages
Considerable attention has been given to equivalence in translating CERAD assessment instruments into foreign languages. Such translations are currently being used in German-speaking populations in Switzerland, Austria, and Germany, and in a standardized national population study in Finland. The following studies showed the French- and English-language versions to be comparable.

Demers P, Robillard A, Lafleche G, et al. Translation of clinical and neuropsychological instruments into French: the CERAD experience. Age Ageing 1994;23:449-451.

Panisset M, Simonetto I, Boller F, et al. Performance of normal elderly subjects using the [English and French versions of the] CERAD neuropsychology battery. In: Poncet M, Michel B, Nieoullon A, eds. Update on AD and related syndromes. Marseille, Solal: 1994:357-359.

Statistics and Data Management
CERAD has developed improved methods for analyzing longitudinal data, which maximize the amount of information provided by a sample with rolling enrollment and different lengths of time in the study. Less conventional approaches to examining data, based on fuzzy set theory, have also been examined.

Edland SD, Grosser S, Barnhart R, et al. Improved efficiency in the relationship between level and slope. American Statistical Association. 1995 Proceedings of the Biometrics Section: 148-153.

Fillenbaum GG, Woodbury M. Typology of Alzheimer's Disease: findings from CERAD data. Aging Mental Health 1998;2:105-127.

Unger J, van Belle G, Heyman A. Cross-sectional vs. longitudinal estimates of cognitive change in the non-demented elderly. J Am Geriatr Soc 1999;47:559-563.

Woodbury MA, Fillenbaum GG. Psychometric characteristics of the Mini-Mental State Examination in patients with Alzheimer's disease: a grade of membership analysis of CERAD data: Part II. Int J Geriatr Psychiat 1996;11:543-553.

Sampling Issues
Characteristics of the measures used and of the study population can influence findings. We found that the widely-used Clinical Dementia Rating Scale is indeed valid. While the most ill patients are more likely to drop out of longitudinal studies of nondemented elderly, studies of persons with AD showed that the most ill are more likely to stay. Continued participation of control subjects who are spouses of enrolled patients is interdependent. Not surprisingly, the continued participation of one is related to the continued participation of the other.

Fillenbaum GG, Peterson B, Morris JC. Estimating the validity of the Clinical Dementia Rating scale: the CERAD experience. Aging: Clin Exp Res 1996;8:379-385.

Peterson B. Re: Association of education with reported age of onset and severity of Alzheimer's disease at presentation: Implications for the use of clinical samples [letter]. Am J Epidemiol 1996;143:1177.

Smith DS, Fillenbaum G. Comparison of spouse and community controls within CERAD. Aging: Clin Exp Res 1994;6:151-157.

Theses and Dissertations
Barnett M. (1992) Standardization of Clinical Dementia Rating (CDR) among 23 Alzheimer's disease study centers. Master's thesis, Department of Biostatistics, University of Washington.

Blazina LB. (1996) Investigation of possible behavioral profiles in Alzheimer's disease. Doctoral dissertation, The Fielding Institute, Santa Barbara, California.

Fisher NJ. (1997) External validation of distinct neuropsychological subgroups of Alzheimer's disease patients: preliminary findings from the CERAD data. Doctoral dissertation, University of Windsor.

Miller S. (1996) Time to nursing home admission for patients with Alzheimer's disease: The effect of healthcare system characteristics. Doctoral dissertation, University of Illinois.

Unger J. (1993) A comparison of longitudinal and cross-sectional rates of decline in MMSE scores in Alzheimer's controls. Master's thesis, Department of Biostatistics, University of Washington.

Yang M. (1993) Cross-cultural comparison of the Mini-Mental State Examination (MMSE) in patients with Alzheimer's disease. Master's thesis, Department of Biostatistics, University of Washington.

Additional Publications
The authors of most of the following papers were not members of the original CERAD group. They have, however, published important studies based on CERAD data and concepts.

Behavioral Studies


Ferris SH, Mackell JA. Behavioral outcomes in clinical trials for Alzheimer disease. Alzheimer Dis Assoc Disord 1997;11 Suppl 4:S10-15.

Perrault A, Oremus M, Demers L, et al. Review of outcome measurement instruments in Alzheimer’s disease drug trials: psychometric properties of behavior and mood scales. J Geriatr Psychiat and Neurology 2000;13:181-196.

Clinical

Henderson VW, Buckwalter JG. Cognitive deficits of men and women with Alzheimer's disease. Neurology 1994; 44:90-96.

Neumann PJ, Araki SS, Arcelus A, et al. Measuring Alzheimer's disease progression with transition probabilities: estimates from CERAD. Neurology 2001;57:951-964.

Olichney JM, Galasko D, Salmon DP. Cognitive decline is faster in Lewy body variant than in Alzheimer's disease. Neurology 1998;51:351-357.

Miller SC, Prohaska TR, Furner SE, et al. Time to nursing home admission for persons with Alzheimer's disease: the effect of health care system characteristics. J Gerontol: Social Sciences 1998;53B:S341-S353.

Epidemiology


Ganguli M, Ratcliff G, Huff FJ. Effects of age, gender, and education on cognitive tests in a rural elderly community sample. Neuroepidemiology 1991;10:42-52.

Guruje O, Unverzagt FW, Osuntokun BO. The CERAD Neuropsychological Test Battery: norms from a Yoruba-speaking Nigerian sample. West African J Med 1995;14:29-33.

Lee DY, Lee JH, Ju YS, et al. The prevalence of dementia in older people in an urban population of Korea: the Seoul study. J Am Geriatr Soc 2002;50:1233-1239.

Liu CK, Lai CL, Tai CT, et al. Incidence and subtypes of dementia in southern Taiwan: impact of socio-demographic factors. Neurology 1998;50:1572-1579.

Riley KP, Snowdon DA, Saunders AM, et al. Cognitive function and apolipoprotein E in very old adults: findings from the Nun Study. J Gerontol Series B-Psychological Sciences & Social Sciences 2000;55:S69-75.

Unverzagt FW, Hui SL, Farlow MR et al. Cognitive decline and education in mild dementia. Neurology 1998;50:181-185.

Neuropathology


Neuropathology Group. Medical Research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community based population. Lancet 2002; 359: 624-625.

Neuropsychology


Stewart R, Richards M, Brayne C. Cognitive function in UK community-dwelling African Caribbean elders: normative data for a test battery. Int J Geriatr Psych 2001; 16:518-527.

Statistical Analyses


Gillen TE, Gregg KM, Yuan H, et al. Clinical trials in Alzheimer’s disease. Calculating Alzheimer Disease Assessment Scale - cognitive subsection with the data from the Consortium to Establish a Registry for Alzheimer’s Disease. Psychopharm Bull 2001;35:83-96.

Mendiondo MS, Ashford JW, Kryscio RJ. Modeling mini-mental state examination changes in Alzheimer's disease. Stat Med 2002;19:1607-16.

Translations


Lee JH, Lee KU, Lee DY, et al. Development of the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease. J Gerontol Series B-Psychological Sciences & Social Sciences 2000;57:P47-53.

Berres M, Monsch AU, Bernasconi F, et al. Normal ranges of neuropsychological tests for the diagnosis of Alzheimer's disease. Studies In Health Technology and Informatics 2000;77:195-199.


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